GLUTAMATE RECEPTORS ACTIVATE CA-2+ MOBILIZATION AND CA-2+ INFLUX INTO ASTROCYTES
GLUTAMATE RECEPTORS ACTIVATE CA-2+ MOBILIZATION AND CA-2+ INFLUX INTO ASTROCYTES
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DOI：
10.1073/pnas.87.9.3454
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
MILLER, RJ
中科院分区：
文献类型：
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作者：
GLAUM, SR;HOLZWARTH, JA;MILLER, RJ
我们测量的变化，在单个星形胶质细胞中的谷氨酸类似物quisqualate（QA）和相关物质的培养物中，通过使用fura-2数字荧光显微镜细胞溶质Ca 2+（[Ca 2 +]i）的摩尔浓度。在从皮层、海马和小脑培养的细胞中，QA类似物α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸酯（AMPA; 10 μ M）引起[Ca 2 +]i的缓慢增加，其幅度适中（约10 μ M）。200 nM）。这些作用被10 μ M 6-硝基-7-氰基-喹喔啉-2，3-二酮（CNQX）完全消除。在小脑星形胶质细胞中，QA产生了类似的效果。然而，在皮质和海马星形胶质细胞中，对QA的反应要复杂得多。在这些细胞中，QA产生初始[Ca 2 +]i尖峰，随后是持续的Ca 2+流入（“平台”）。在细胞外Ca 2+的情况下，这一平台被废除，但穗仍然存在。CNQX不阻断尖峰，仅略微减小某些细胞中的平台的大小。Ni 2+（10 μ M）而不是尼莫地平（10 μ M）降低了平台的幅度。用100 nM佛波醇12-肉豆蔻酸酯13-乙酸酯预处理15 min可消除QA响应的尖峰，但不能消除QA响应的平台部分。用250 ng/ml百日咳毒素处理12-16小时未能改变反应。在某些情况下，QA响应的潜伏期对于组中的单个细胞而言差异很大。似乎反应开始于一个细胞，然后扩散到邻近的细胞。因此，QA似乎触发了复杂的反应，在一些星形胶质细胞组成的Ca 2+动员从细胞内的商店和Ca 2+流入AMPA敏感和不敏感的途径的激活。
We measured changes in the molar concentration of cytosolic Ca2+ ([Ca2+]i) in individual astrocytes in culture produced by the glutamate analog quisqualate (QA) and related substances by using fura-2 digital fluorescence microscopy. In cells cultured from the cortex, hippocampus, and cerebellum, the QA analog .alpha.-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA; 10 .mu.M) produced a slow increase in [Ca2+]i that was modest in amplitude (.apprxeq. 200 nM). These effects were completely abolished by 10 .mu.M 6-nitro-7-cyano-quinoxaline-2,3-dione (CNQX). In cerebellar astrocytes, similar effects were produced by QA. However, in cortical and hippocampal astrocytes, the response to QA was much more complex. In these cells, QA produced an initial [Ca2+]i spike that was followed by a sustained influx of Ca2+ ("plateau"). In the absence of extracellular Ca2+, this plateau was abolished but the spike remained. CNQX did not block the spike and only slightly reduced the size of the plateau in some cells. Ni2+ (10 .mu.M) but not nimodipine (10 .mu.M) reduced the amplitude of the plateau. Pretreatment with 100 nM phorbol 12-myristate 13-acetate for 15 min abolished the spike but not the plateau portion of the QA response. Treatment with pertussis toxin at 250 ng/ml for 12-16 hr failed to alter the response. In some instances, the latency of the QA response differed considerably for individual cells in a group. It appeared that the response began in one cell and then spread to neighboring cells. Thus, QA appears to trigger a complex response in some astrocytes consisting of Ca2+ mobilization from intracellular stores and also Ca2+ influx resulting from the activation of AMPA-sensitive and -insensitive pathways.